JAK-1 Inhibitors - The Next Advancement for the Management of RA?
by C.H. Weaver M.D. (08/2018)
The investigational agent (Upadacitinib) ABT-494, a JAK-1 inhibitor has been reported to be effective for the management of refractory moderate-to-severe rheumatoid arthritis (RA) in two clinical studies.
Janus-associated kinase 1 (JAK1) inhibitors mediate the signaling of cytokines and growth factors important for blood cell production and immune function. Jakafi® (ruxolitinib) a JAK 1 inhibitor is currently approved for the treatment of some Myleoproliferative Neoplasms. Blocking the JAK pathway also appears important for treating the immune response in RA and investigators have begun to report results. AbbVie is developing ABT 494 in RA and has released some early results from their Balance I and II clinical studies.
In the BALANCE-I study, 276 RA patients who had previously had an inadequate response to one or more tumor necrosis factor (TNF) inhibitors received one of four doses of ABT-494 or placebo for 12 weeks. A 20% or greater improvement was seen in a significant proportion of patients in all dosage groups compared to those treated with placebo.
In the BALANCE-II study, 300 RA patients who had experienced an inadequate response to methotrexate were given one of five doses of ABT-494 for 12 weeks, and a significant improvement was reported in all but the lowest dose group.
ABT-494 has the potential to become a useful treatment option for some of the most challenging RA patients, those that have an inadequate response to TNF drugs.
Overall ABT-494 was generally well tolerated and he most common reported side effect was headache, which was reported by fewer than 5% of patients.